Bonelli was born in 1932 in Milan. He was the son of Gian Luigi Bonelli, the popular co-creator of the hugely successful Tex Willer character featured in Tex, a series that launched in the late '40s when Sergio was a teenager.

Bonelli began writing comics in 1957 under the name Guido Nolitta. The pen name was initially used to afford Bonelli some professional distance from his famous father, but continues to be utilized in a variety of places even though Bonelli's identity behind the pseudonym is well known. His first gig was a translation of the series Verdugo Ranch from Spanish in to Italian. His first original series was Un ragazzo nel Far West, with artist Franco Bignotti. By the early 1960s Bonelli began to find his level, writing several installments in the Little Ranger series, co-creating with artist Sergio Tarquinio the series Il Guidice Bean and most importantly becoming the co-creator of the character Zagor in 1961.

Zagor was an imaginative western set in the 1820s in a fictional Pennsylvania forest, featuring a kind of folk-legend, larger than life character that fought to keep the peace throughout his largely untamed home territory. In addition to hitting elements of the still-popular western genre, the serial wasn't afraid to fold in elements of other genres, most memorably science fiction. The series proved tremendously popular in Eastern Europe, and Turkey's film industry produced three unofficial movies in the 1970s. The character joined Tex Willer in comics published in the Greece and Israel markets. Bonelli wrote Zagor's adventures until 1980, making him the series' primary writer on 182 issues of the character's lengthy saga, as well as stories for a half dozen or so special editions.

The writer enjoyed a massively successful concurrent career as an editor and eventually publisher with the company CEPIM, the company that eventually became Sergio Bonelli Editore. He's credited with cementing the popular 96-page Italian comics format and within the bounds of genre adventure making sure his line offered up a variety of characters and concepts. Primary among the big hits that arrived under his editorial run was the hugely popular Dylan Dog from writer Tiziano Sclavi, which debuted in 1986. Other hits for the company, of the many that thrived under Bonelli's apparent editorial strategy of leaving his creators alone to make comics as they saw fit, were Nathan Never and Martin Mystère.

Bonelli remained a potent creator in his own right. He co-creadted the Mister No series in 1975, and wrote a number of that decade's Tex stories. In 1990, he co-created the series River Bill with Francesco Gamba.

Bonelli was hospitalized for a week before he passed away. The exact cause of death has not been released.

Sergio Bonelli is survived by a wife Beatrice and a son David, both of whom were reportedly with him at the moment of his passing. David works at the publisher bearing his father's name. The web site of the publishing company that bore his name is allowing fans to post messages. They've announced a funeral for September 29 at the Chapel of the Monumental Cemetery in Milan.